Below is a link to a page that provides comprehensive regularly updated info written by two ALK research oncologists Dr. Alice Shaw and Ben Solomon, Phd (then edited by three people). It is written for an audience of doctors and other professionals so it can get technical, but generally I believe most people will be able to understand the key ideas.

Roche (Genentech) announced on June 6, 2017 at the 2017 ASCO conference that the have results from their first line Phase 3 Global Trial that Alectinib had a median PFS of 25.7 months vs 10.4 months for Crizotinib (over a year longer). The trial also found that Alectinib reduced the risk of cancer progression or death by 53% vs. Crizotinib. Furthermore, at 12 months the incidence of brain metastases was 9% for Alectinib and 41% for Crizotinib. Serious side effects were marginally better with Alectinib.

These results compliment earlier results from a Japan only trial and are likely to be the basis of FDA Application to move Alectinib to the first line setting.

I strongly recommend reading the New England Journal of Medicine (NEJM) article. The charts on page 6 are particularly persuasive.

As of May 26, 2017 the FDA approved ceritinib for first line use. So it will go head to head with crizotinib. One article said a similar EU approval was likely “in coming weeks”.

The results are based on the phase 3 ASCEND-4 trial which found that in the first line setting that patients who took ceritinib had a median progression-free survival of 16.6 months vs. 8.1 months on Pemetrexed platinum chemotherapy.

On April 27, 2017, the FDA granted Pfizer Breakthrough Status on lorlatinib for patients previously treated with one or more ALK inhibitors. So you don’t have to take Crizotinib first, any of the other 3 will do. Also a Phase 3 CROWN study (NCT03052608) has begun enrolling patients.

As of March 6, 2017, ClinicalTrials.gov lists a Trial of TPX-0005 which targets ALK, ROS1, and NTRK 1-3. At this time there are four trial sites at: UC Irvine Cancer center, University of Colorado, Denver, Massachusetts General Hospital, and Memorial Sloan Kettering.

The trial does cover patients with regular body measurable mets and only measurable brain mets.

As of August 30, 2016 Arriad had filed its new drug application with the FDA for brigatinib. As of Oct 31, 2016 the FDA granted ARIAD’s request for Priority Review and has set an action date of April 29, 2017.

As of January 9, 2017 Ariad agreed to be bought by Takeda Pharmaceutical Company Limited, a Japanese company. The merger is expected to close by the end of February 2017.

In Phase III study by Novartis on Zykadia® (ceritinib) as a first-line treatment, they found a 45% reduction in the risk of disease progression. The study found a median progression free survival (PFS) of 16.6 months for all patients taking ceritinib, compared with 8.1 months for patients treated using just chemotherapy. Also reported an ORR of 72.5%, compared with 26.7% for chemotherapy patients. Patients with no brain metastases had a median PFS of 26.3 months with Zykadia compared with 8.3 months for standard chemotherapy.

Ariad had positive info from a Phase I/II study and a pivotal phase 3 ALTA trial studying brigatinib, in patients with brain metastases. Patients with brain mets had an ORR was 53% in the Phase I/II trial.

The patients previously treated with Crizotinib and with brain mets had an ORR of 67% in the higher dose arm B of the ALTA trial. Median brain mets PFS in Arm B was 18.4 months.

Arm A (90 mg) median Progression Free Survival (PFS) increased from 8.8 months to 9.2 months. For arm B (180 mg) the median PFS increased from 11.1 months to 12.9 months. Probability of overall survival at 1 year was 71% for arm A and 80% for arm B.

For patients with measurable brain mets at baseline, for arm A the Objective Response Rate was 36% and for arm B the ORR was 67%. Median intracranial PFS was 15.6 months for arm A and not yet reached for arm B.